6-30577864-A-T

Variant names:

• chr6-30577864-A-T
• rs1801585067
• NM_001025091.2:c.167A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025091.2(ABCF1):​c.167A>T​(p.Glu56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCF1 NM_001025091.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62

Genes affected

ABCF1 (HGNC:70): (ATP binding cassette subfamily F member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12291047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCF1	NM_001025091.2	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 24		NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 25	1	NM_001025091.2	ENSP00000313603.8
ABCF1	ENST00000376545.7	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 24	1		ENSP00000365728.3
ABCF1	ENST00000441867.6	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 25	5		ENSP00000405512.2
ABCF1	ENST00000468958.1	c.-125A>T		5_prime_UTR_variant	Exon 2 of 7	3		ENSP00000440893.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727176

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167A>T (p.E56V) alteration is located in exon 3 (coding exon 3) of the ABCF1 gene. This alteration results from a A to T substitution at nucleotide position 167, causing the glutamic acid (E) at amino acid position 56 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T;.;T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.13	T;T;D
Polyphen		0.16	B;.;.
Vest4		0.38
MutPred		0.066		Loss of methylation at K60 (P = 0.074);Loss of methylation at K60 (P = 0.074);Loss of methylation at K60 (P = 0.074);
MVP		0.70
MPC		0.38
ClinPred		0.80	D
GERP RS		5.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1801585067; hg19: chr6-30545641;